Immunologic events occurring in acute Hepatitis C Virus infection have not been well defined, nor have the mechanisms through which HCV establishes persistence in most individuals. The frequency with which individuals with acute HCV exposure mount protective or "clearing" immune responses is not known. Correlation of host cellular and humoral immune responses with subsequent virologic and clinical outcomes in a cohort of HCV exposed individuals could provide valuable insights for ongoing efforts to develop an effective HCV vaccine. Health care workers in urban hospitals are at significant risk for HCV exposure when needlestick events occur. Clinical studies performed to date suggest that risk of HCV transmission lies between 0-6% to 10% of episodes (HCV antibody +, vs. HCV PCR+ source patients, respectively). At the University of Maryland Medical System, 25-50 percutaneous HCV exposures occurred each year between 1994-1996. Similar HCV needlestick exposure rates have been reported at other Baltimore hospitals. Acute symptomatic HCV transmission has been observed. The application proposes to create an infrastructure to support detailed immunological and virological studies of individuals exposed to HCV through needlestick events. A coalition of Infection Control and Employee Health professionals at collaborating Baltimore hospitals will prospectively identify and enroll individuals with HCV exposure. Approximately 100 at-risk individuals will be enrolled each year, with specimen collection at seven time points during the initial 6 months of follow-up. At scheduled phelbotomy, plasma and peripheral blood mononuclear cells will be collected and appropriately stored. A clinical data base, anonymously linked to the specimen repository, will be created. These reagents will be made available for investigations of HCV pathogenesis.